10-11-22 – Vaccinations and Immunisations Flashcards
Learning outcomes
- Describe the main types of vaccine preparations in use
- Describe the advantages of vaccination
What are the 3 parts of the Pasteur principle?
- 3 parts of the Pasteur principle:
1) Isolate pathogen
2) Inactivate pathogen
3) Inject pathogen - This principle is still largely used
What are 6 essential characteristics of vaccines?
- 6 essential characteristics of vaccines:
1) Must provide effective protection without risk of causing disease or severe side effects
2) Protection should be long-lived (may use boosters)
3) Should stimulate correct arm of immune response, ie antibodies or effector T cells
4) Stimulate neutralising antibodies to prevent reinfection
5) Stable for long-term storage and transport
6) Economically affordable for widespread use
What are the 6 different types of vaccines?
What type of organisms might each be used for?
- 6 different types of vaccines:
1) Live
* Organisms capable of normal infection and replication.
* Not used against pathogens that can cause severe disease
2) Attenuated
* Organism is live, but ability to replicate and cause disease reduced by chemical treatment or growth-adaptation in non-human cell lines (measles, mumps, rubella)
3) Killed
* Organism killed by physical or chemical treatment.
* Incapable of infection or replication, but still able to provoke strong immune response (B.pertussis, typhoid)
4) Extract
* Materials derived from disrupted or lysed organism, e.g capsular polysaccharides (usually most immunogenic part)
* Used when risk of organism surviving inactivation steps (flu, pneumococcal, diphtheria, tetanus)
5) Recombinant
* Genetically engineered to alter critical genes.
* Often can infect and replicate but does not induce associated disease
6) DNA
* Naked DNA injected.
* Host cells pick up DNA and express pathogen proteins that stimulate immune response
* Injecting Mrna for covid spike proteins on its own can provide protective immune responses
What is the most effective type of vaccine?
Why is this?
How does safety affect vaccine efficacy?
- The most effective vaccines have been live or attenuated
- This is because living or attenuated organisms express proteins and stimulate the immune response in a manner which most closely resembles normal infection
- Paradoxically, the safer the vaccine, the less effective some have been
What is herd immunity?
What does this result in?
How can this affect vaccination rates?
What can this cause?
Does everyone need to be immunised? Why is this?
- Herd immunity is resistance to the spread of an infectious disease within a population that is based on pre-existing immunity of a high proportion of individuals as a result of previous infection or vaccination.
- This results in the beneficial impact of vaccination being so clear that some people are no longer aware of dangers of diseases
- This can actually result in reduced rates of vaccination and also public debate on whether side-effects occur, eg MMR
- This can cause a pool of unimmunised individuals to be created which can become victim to disease. Measles has increased probably because of this.
- Possibly not everyone needs to immunised.
- If enough are vaccinated then the chances of an unprotected person meeting a pathogen becomes small. The population remain essentially resistant
What is the DTaP/IPV/Hib vaccine for?
What is the Men C vaccine for?
What is the DTaP/IPV vaccine for?
What is the Td/IPV vaccine for?
What are different ages at which certain vaccinations are given (in diagram)?
- Vaccines and their definitions:
1) DTaP/IPV/Hib
* Diphtheria, Tetanus, Pertussis,
* Inactivated Polio vaccine
* Haemophilus influenzae type B
2) Men C
* Meningococcal C conjugate
3) DTaP/IPV
* Booster vaccine for diphtheria, tetanus, pertussis, and Inactivated Polio vaccine
4) Td/IPV
* Booster vaccine for tetanus, diphtheria, inactivated polio vaccine
When are pneumococcal and flu vaccines offered?
How many flu vaccines are available?
- The Pneumococcal vaccine is offered to 65yr and over individuals
- The flu vaccine is offered to elderly and at-risk individuals.
- In region of 11 million plus people in recommended groups, 14 million doses available.
When are travel vaccinations changing?
What are 3 examples of travel vaccination recommendations from 2005?
- Travel vaccinations are constantly changing
- 3 examples of travel vaccination recommendations from 2005:
1) Avian Flu, West Nile Virus (USA, Canada and Portugal)
2) Marburg Virus (Angola)
3) Poliomyelitis (Nigeria)
What is reverse vaccinology?
Why was this useful for meningococcus B?
- Reverse vaccinology is the technique of identifying the protein exposed on the surface of pathogens by sequencing their genome in order to find new vaccines
- Originally, the microorganism itself was used to create vaccines
- This is useful for Meningococcus B, because the capsular polysaccharide antigen that would normally be a good target looks almost identical to a sugar on NCAM, an important neuronal membrane protein.
- Antibodies could cause autoimmunity due to this
- Reverse Vaccinology for MenB:
1) Whole bacterial genome sequenced
2) 600 candidate genes identified
3) 350 expressed in E.coli bacteria in lab
4) 344 proteins purified and used to generate antisera in mice
5) 91 novel surface molecules identified
6) 28 bactericidal sera identified
7) 5 vaccine candidates in clinical trials
8) Total time: 24-36 months.
What are examples of challenges in development of vaccinations?
- Examples of challenges in development of vaccinations:
1) 1918: Spanish Flu, 20-40 million dead
2) 1957: Asian Flu, 1-4 m dead
3) 1968: Hong Kong, 4m dead
4) Latest potential threat is H5N1.
* First reappeared HK 1997, infected 18, killed 6.
* Multiple cases in Far East
* 100 million fowl culled to prevent spread.
5) SARS coronavirus: Feb to July 2003
* infected 8,098 people, killed 774.
6) West Nile Virus: NY 1999
* Within 4 years spread across most of USA, infected 9,862 people, 264 deaths in 2003
What are 4 origins of new vaccination challenges?
- 4 origins of new vaccination challenges:
1) HIV: nonhuman primate origin
2) Ebola: handling of gorilla, chimp, duikers (bush meat)
3) SARS: palm civets and racoon dogs (animal markets)
4) vCJD: food chain, rendering.
What do vaccines have to engage in the immune system?
What do dendritic cells express?
How do dendritic cells work?
- It is important that there is a strong dendritic cell activation in the immune system from vaccines
- Dendritic cells express Pattern Recognition Receptors (PRR), members of the Toll-like receptor Family (TLR)
- When dendritic cells meet something pathogenic, they grab a hold of the pathogen, and move it to the lymph node to start the process of activating T and B cells
- This results in a big upregulation of the immune response
What do the 11 Toll-like receptors (TLRs) bind to?
What is commonly used in vaccines?
What are these called? What is their purpose?
- What the 11 Toll-like receptors (TLRs) bind to:
1) TLR1: lipopeptides
2) TLR2: lipopeptides
3) TLR3: dsRNA
4) TLR4: Lipopolysaccharide, heat shock proteins
5) TLR5: flagellin
6) TLR6: lipoproteins
7) TLR7: ?
8) TLR8: ssRNA
9) TLR9: CpG (cytosine-phosphate-guanosine, bacterial DNA
10) TLR10: ?
11) TLR11: bacterial components.
- Purified or synthetic Lipopolysaccharides are commonly used in vaccines
- This will stimulate the TLR4 receptor and kickstart the immune system
- This is known as an adjuvant being added to the vaccines, which stimulates the immune system
Are dendritic cells (DC) innate or adaptive immunity?
What does activation of DCs increase?
What is CpG?
What does it help stimulate? What is IFN gamma?
- Dendritic cells (DC) sit at the interface between innate immunity and specific (adaptive) immunity
- Activation of DC’s vastly increases their ability to capture and process antigen and immunogens, and also attract and activate T cells.
- CpG is an adjuvant that can be used in HepB or flu vaccines
- When used, it helps stimulate increase antibody production of IFN-gamma secretion
- Interferon‐gamma (IFN‐γ) is a cytokine that plays an important role in inducing and modulating an array of immune responses
